Rashmi Rao

Gestational Diabetes, Preeclampsia and Cytokine Release: Similarities and Differences in Endothelial Cell Function

Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy affects the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. Similarly, some but not all studies have suggested that infection of the mother under certain circumstances can also lead to preeclampsia as women with either a bacterial or viral infection were at a higher risk of developing preeclampsia, compared to women without infection and infection also leads to a release in TNFα. Endothelial cells exposed to either high glucose or TNFα leads to an increase in the production of H2O2 and to a decrease in endothelial cell proliferation. The cellular and molecular mechanisms involved in this phenomenon are discussed.Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy has profound effects on the fetus and long term effects on the neonate. All three conditions affect the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. It has also been suggested although not universally accepted that under certain circumstances maternal infection may also predispose to pre-eclampsia. Pre-eclampsia is also associated with the release of TNFα and endothelial dysfunction. However, the cellular and molecular mechanism(s) leading to the endothelial dysfunction by either hyperglycemia or by the cytokine TNFα appear to be different. In this chapter, we explore some of the similarities and differences leading to endothelial dysfunction by both hyperglycemia and by the inflammatory cytokine TNFα and the cellular and molecular mechanism(s) involved.

The value of the first trimester ultrasound in the era of cell free DNA screening

To describe the clinically relevant findings detected by the first trimester ultrasound (FTU) and to determine the additional value of the FTU compared to cell free DNA (cfDNA) alone.

Endothelial Cell Function in Utero-placental Circulation Physiology and Pathophysiology

Endothelial cells in the utero-placental circulation play an important physiological role in maintaining the fetoplacental vessels in a vasodilated state as these vessels are non-innervated. These endothelial cells produce both prostacyclin and nitric oxide which in addition to causing vasodilation also prevent platelet aggregation and adhesion of platelets to endothelial cells. Most investigators are of the opinion that energy metabolism of endothelial cells and ATP generation is mainly glycolytic. Glycolytic activity in endothelial cells is increased during proliferation to maintain ATP at normal levels by an increase in the expression of the glucose transporter. More recent studies have reported the existence of a functional F1F0 ATP synthase on the surface of HUVEC and it has been found to be enzymatically active in the synthesis of ATP. Additional studies utilizing very early passage HUVEC need to be carried out to ascertain the relative contribution of oxidative phosphorylation compared with the glycolytic pathway for ATP synthesis in normal pregnancy as well as in abnormal states like preeclampsia, diabetes, intrauterine injection as well as intrauterine growth restriction.

Clinical accuracy of abnormal cell‐free fetal DNA results for the sex chromosomes

To investigate factors associated with abnormal cell‐free DNA (cfDNA) results for sex chromosomes (SCs).

Zika Risk and Pregnancy in Clinical Practice: Ongoing Experience as the Outbreak Evolves

OBJECTIVE To describe a single U.S. perinatal centers ongoing experience with evaluating pregnant patients with potential exposure to Zika virus infection. METHODS This is an institutional review board-approved longitudinal observational study from January to August 2016 from a single perinatal referral center. Patients who had traveled to or had sexual contact with a person who traveled to a region with documented local Zika virus transmission were included in the study. The aim of the study was to identify the rate of confirmed infection among pregnant women referred to our center with established risk factors for Zika virus acquisition. We also sought to characterize travel patterns that constituted risk, to identify rates of symptoms suggesting infection, and to potentially describe findings suggestive of congenital Zika virus infection in prenatal ultrasound evaluations. RESULTS We evaluated 185 pregnant women with potential Zika virus exposure. Testing was offered in accordance with the version of the Centers for Disease Control and Prevention guidelines in place at the time of the consultation visit. Geographic exposure data showed Mexico (44%), the Caribbean (17%), North America (16%), South America (13%), and Central America (9%) to be the most common areas in which potential exposure occurred. One hundred twenty-three (67%) patients reported insect bites and 19 (10%) patients reported symptoms. Overall, five (3% of all) patients had prenatal ultrasound findings suggestive of possible fetal Zika virus infection; all their Zika virus test results returned negative. These findings included microcephaly, echogenic intracardiac foci, and ventricular calcifications. Of the 153 Zika virus screening tests ordered, eight (5%) immunoglobulin M results returned positive or equivocal with only one positive through confirmatory testing. Overall, 1 of 185 (0.5%) of all those consulted and 1 of 153 (0.7%) of those tested had a confirmed Zika virus infection with no confirmed fetal or neonatal infections. CONCLUSION We identified low rates of confirmed maternal Zika virus infection in our cohort, but the number of patients described here demonstrates the magnitude of concern existing among both patients and physicians regarding possible perinatal Zika virus infection. It also underscores the need for health care providers to be prepared to answer questions, explain laboratory and ultrasound results, and describe testing options for concerned patients and their families.

Maternal and neonatal outcomes after antenatal corticosteroid administration for PPROM at 32 to 33 6/7 weeks gestational age*

Abstract Background: Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids. Study design: We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed. Results: Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p = 0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p = 0.001). There was no difference in chorioamnionitis or RDS. Conclusion: In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM.

Standardized Six-Step Approach to the Performance of the Focused Basic Obstetric Ultrasound Examination.

OBJECTIVES This study aims to validate the feasibility and accuracy of a new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, and compare the new approach to the regular approach performed in the scheduled obstetric ultrasound examination. STUDY DESIGN A new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, to evaluate fetal presentation, fetal cardiac activity, presence of multiple pregnancy, placental localization, amniotic fluid volume evaluation, and biometric measurements, was prospectively performed on 100 pregnant women between 18(+0) and 27(+6) weeks of gestation and another 100 pregnant women between 28(+0) and 36(+6) weeks of gestation. The agreement of findings for each of the six steps of the standardized six-step approach was evaluated against the regular approach. RESULTS In all ultrasound examinations performed, substantial to perfect agreement (Kappa value between 0.64 and 1.00) was observed between the new standardized six-step approach and the regular approach. CONCLUSION The new standardized six-step approach to the focused basic obstetric ultrasound examination can be performed successfully and accurately between 18(+0) and 36(+6) weeks of gestation. This standardized approach can be of significant benefit to limited resource settings and in point of care obstetric ultrasound applications.

P19.06: Increased intertwin discrepancy in cerebroplacental ratio (CPR-Δ) is predictive of earlier age at delivery in monochorionic-diamniotic (MCDA) twins: Poster discussion hub abstracts

Objectives: To investigate the role of CPRfor the prediction of gestational age (GA) of delivery in MCDA pregnancies. Methods: This was a retrospective cohort study of all MCDA pregnancies at a maternal fetal medicine referral centre between 1/2007-2/2017. Exclusion criteria were structural or chromosomal anomalies, intrauterine fetal demise (IUFD) < 16 weeks, or referral after development of Twin–twin transfusion syndrome (TTTS) or twin anemia polycythemia sequence (TAPS). Ultrasounds were performed biweekly from 16-37 weeks to survey umbilical artery (UA) and middle cerebral artery (MCA) Dopplers. CPR was calculated as MCA-PI:UA-PI. CPRwas defined as the absolute difference between the twins and calculated at each visit. The maximum CPRin both the second and third trimester were assessed as predictors of adverse birth outcomes by logistic regression analysis. Pearson’s correlation coefficients were calculated to assess the relationship between CPRand birth outcomes. Results: 143 MCDA twin pregnancies (16 were lost to follow up) and 249 newborns met inclusion criteria: 16 pregnancies (11.2%) were complicated by TTTS, 7 (4.9%) were complicated by TAPS, 41 (28.7%) were complicated by sIUGR, and 8 (5.6%) developed an IUFD of one twin. Mean GA at delivery was 34.9 weeks, of which 73.4% were via Caesarean. Mean birth weight was 2157 g (range: 540 g-3980 g), and 76 (58.7%) pregnancies had NICU admission of at least one twin. There was a significant correlation between maximum CPRin the second trimester to GA at delivery (r = -0.2955, p = 0.0017) and average birth weight (r = -0.3778, p < 0.0001). Logistic regression analysis showed a significant association between maximum CPRin the second trimester and NICU admissions (OR 3.94, 95% CI 1.31-11.85; p = 0.0146). Conclusions: In MCDA twin pregnancies, increasing intertwin CPRis correlated with earlier GA at delivery, lower average birth weight, and NICU admissions. CPR evaluation may be of clinical utility in the surveillance of MCDA twin pregnancies.

P19.09: Regional differences in the management of monochorionic diamniotic (MCDA) twins complicated by Twin-twin transfusion syndrome (TTTS): Poster discussion hub abstracts

Objectives: To elucidate regional differences in management of MCDA pregnancies complicated by TTTS from Facebook (FB) group members. Methods: This was a cross-sectional survey of members of a Facebook (FB) group called ‘‘MoDi Twins’’. REDCAP survey was posted for five days with daily reminders. Participants were collected through ‘‘snowballing,’’ whereby individuals shared the survey to assist with recruiting. Data was analysed using Stata to explore provider type, frequencies of ultrasound screening, treatments and pregnancy outcomes. Categorical variables were analysed using Chi-squared using a p-value of < 0.05. Results: The survey was completed by 2,169 (63% of clicks) subjects, of which 486 (22.4%) were complicated by TTTS. Eighty (16.5%) were diagnosed <16 weeks, 259 (53.5%) between 17-26 weeks and 140 (28.9%) >27 weeks or during labour. Biweekly surveillance resulted in more diagnoses of TTTS at the extremes of GA, when compared to monthly surveillance: at <16 weeks (18.1% versus 8.3%, p<0.001) and > 27 weeks (31.2% versus 18.7%, p<0.001). Regarding treatment of TTTS, 206 (42.5%) had laser ablation, 33 (6.8%) had amnioreduction, and 120 (24.7%) were delivered upon diagnosis. Treatment was performed in stage 1, 2, 3, 4 and 5 in 31.4%, 21.6%, 30.0%, 11.2% and 5.8%, of cases, respectively. Method of treatment had no effect on take home baby rate (p=0.268). MFM involvement in care was associated with a higher take-home baby rate of 73.1% for both and 95.8% of at least one infant, compared to 66.6% and 81.1% with CNM or OB care (p=0.001). Conclusions: The management of TTTS in MCDA gestations varies widely by region and provider type. Guideline recommended biweekly screening increased diagnosis of TTTS at extremes of gestational age, but did not change rate of diagnoses between 17-26 weeks. MFM involvement in care was associated with the highest take-home baby rate in MCDA pregnancies complicated by TTTS.

OC07.08: Variations in antenatal surveillance and patient education in monochorionic-diamniotic (MCDA) twins

Methods: 298 patients with DTT via IVF-ET from January 2012 to December 2016 were retrospectively analysed. These cases were divided into group A (reduced to MS, n = 84), group B (reduced to MDT, n = 149) and group C (without MFPR, n = 65). Group A and B received MFPRs at the 11-13+6 gestational weeks. Fetuses of group C were alive during this time. Results: The live birth rate was higher in group A than B and C (90.50% vs 87.20% vs 86.20%), but with no significance (P > 0.05). Compared with group B, group A had significantly lower rates of premature delivery (11.90% vs 51.70%, P < 0.001), perinatal mortality (5.00% vs 13.40%, P = 0.037), Caesarean section (CS, 66.30% vs 82.10%, P = 0.007) and low birthweight (LBW, 9.20% vs 59.00%, P < 0.001); the gestational age (GA) at delivery (37.9 ± 3.8 vs 35.0 ± 4.2 weeks, P < 0.001) and the live birthweight (3167.8 ± 557.1 vs 2350.8 ± 483.5 g, P < 0.001) were significantly higher in group A. Compared with group C, group A had significantly lower rates of premature delivery (11.90% vs 89.20%, P < 0.001), perinatal mortality (5.00% vs 15.80%, P = 0.015), CS (66.30% vs 83.60%, P = 0.020) and LBW (9.20% vs 92.90%, P < 0.001); the GA at delivery (37.9 ± 3.8 vs 32.8 ± 3.7 weeks, P < 0.001) and the live birthweight (3167.8 ± 557.1 vs 1863.4 ± 409.8 g, P < 0.001) were significantly higher in group A. The rates of preterm delivery (51.70% vs 89.20%, P < 0.001) and LBW (59.00% vs 92.90%, P < 0.001) in group B were significantly lower compared with group C. Conclusions: Both MFPR of DTT to MS and to MDT could obtain better pregnancy outcomes than DTT without reduction. The perinatal pregnancy of MS was better than MDT.